A Phase 2 Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and Safety of BHV-4157 in Patients With Mild to Moderate Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 350
- 试验地点
- 44
- 主要终点
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Total Score at Week 48
研究概览
简要总结
Preclinical models suggest that riluzole, the active metabolite of BHV-4157, may protect from AD-related pathology and cognitive dysfunction. Titrated dose of BHV-4157 to 280 mg, or placebo, were administered orally once daily. Duration of treatment is 48 weeks in double-blind phase. There is also a screening period of up to 42 days; and a 4-week post-treatment observation period. Eligible participants who completed the double-blind treatment phase had the opportunity to receive open-label troriluzole for up to 48 weeks in an open-label extension (OLE) phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 50 to 85 (inclusive) at screening
- •Diagnosed with probable Alzheimer's disease dementia: Core clinical criteria in accordance with NIA/Alzheimer's Association Guidelines.
- •Living in the community (includes assisted living facilities, but excludes long-term care nursing facilities).
- •Ambulatory, or able to walk with an assistive device, such as a cane or walker.
- •Participants must have a study partner who has frequent interaction with them (approximately >3-4 times per week), will be present for all clinic visits, and can assist in compliance with study procedures.
- •An Mini-Mental State Examination score of 14 to 24, inclusive, at screening.
- •A brain MRI scan within 6 months of screening consistent with a diagnosis of Alzheimer's disease.
- •Participants should be treated with a stable dosage regimen of FDA-approved AD medications (acetylcholinesterase inhibitors (AchEI) and/or memantine) for at least 3 months prior to screening. Participants should be expected to remain on a stable dosage regimen of these medications for the duration of the trial.
- •Participants who are not being treated with FDA-approved AD medications at the time of screening, because they have contraindications to these medications, or because they have previously failed treatment with these medications, are also eligible for inclusion, if it is expected that they will not be treated with these medications for the duration of the trial.
排除标准
- •Hepatic impairment defined as Child-Pugh class of A or more severe liver impairment.
- •Other neurodegenerative diseases and causes of dementias, including Parkinson's disease and Huntington's disease, vascular dementia, CJD (Creutzfeldt-Jakob disease), LBD (Lewy Body dementia), PSP (Progressive Supranuclear Palsy), AIDS (Acquired Immunodeficiency Syndrome), or NPH (normal pressure hydrocephalus).
- •History of a major depressive episode within the past 6 months of screening.
- •Insulin-dependent diabetes or uncontrolled diabetes with HbA1c value >8.0 %.
- •Cancer or a malignant tumor within the past 3 years, except patients who underwent potentially curative therapy with no evidence of recurrence for >3 years. Patients with stable prostate cancer or non-melanoma skin cancers are not excluded.
- •Participation in another clinical trial for an investigational agent and having taken at least one dose of study medication, unless confirmed as having been on placebo, within 12 weeks prior to screening. The end of a previous investigational trial is defined as the date of the last dose of an investigational agent.
研究组 & 干预措施
BHV-4157
troriluzole, 280 mg (2 x 140 mg) capsules, QD
干预措施: troriluzole (Drug)
Placebo
matching 280 mg (2 x 140 mg) placebo capsules, QD
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Total Score at Week 48
时间窗: Baseline (Day 1) and Week 48
The ADAS-Cog is a structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing a letter in an envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions were also obtained. The test was scored in terms of errors on a scale ranging from 0 (best) to 70 (worse), with higher scores indicate poorer performance and greater impairment.
Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-Sum of Boxes) Total Score at Week 48
时间窗: Baseline (Day 1) and Week 48
The CDR-sum of boxes is a validated composite rating of cognition and everyday functioning used in longitudinal AD research which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview 3 cognitive domains including memory, orientation, and judgement/problem solving and 3 everyday functional domains including community affairs, home and hobbies and personal care. The individual domain score ranging from 0 (none) to 3 (severe) but the scores in each of these were combined to obtain a composite score (sum of boxes) ranging from 0 (best) to 18 (worst), with higher scores indicate poorer performance and greater impairment. The individual domain scores are added to create a sum of the box scores.
次要结局
- Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score at Week 48(Baseline (Day 1) and Week 48)
- Change From Baseline in Mini-Mental Status Examination (MMSE) Total Score at Week 48(Baseline (Day 1) and Week 48)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs(TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks.)
- Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 48(Baseline (Day 1) and Week 48)
- Change From Baseline in Magnetic Resonance Imaging (MRI) Hippocampal Volume at Week 48(Baseline (Day 1) and Week 48)